Abstract

Background

As a key parameter of genome sequence variation, the GC content of bacterial genomes
has been investigated for over half a century, and many hypotheses have been put forward
to explain this GC content variation and its relationship to other fundamental processes.
Previously, we classified eubacteria into dnaE-based groups (the dimeric combination
of DNA polymerase III alpha subunits), according to a hypothesis where GC content
variation is essentially governed by genome replication and DNA repair mechanisms.
Further investigation led to the discovery that two major mutator genes, polC and dnaE2, may be responsible for genomic GC content variation. Consequently, an in-depth analysis
was conducted to evaluate various potential intrinsic and extrinsic factors in association
with GC content variation among eubacterial genomes.

Results

Mutator genes, especially those with dominant effects on the mutation spectra, are
biased towards either GC or AT richness, and they alter genomic GC content in the
two opposite directions. Increased bacterial genome size (or gene number) appears
to rely on increased genomic GC content; however, it is unclear whether the changes
are directly related to certain environmental pressures. Certain environmental and
bacteriological features are related to GC content variation, but their trends are
more obvious when analyzed under the dnaE-based grouping scheme. Most terrestrial,
plant-associated, and nitrogen-fixing bacteria are members of the dnaE1|dnaE2 group,
whereas most pathogenic or symbiotic bacteria in insects, and those dwelling in aquatic
environments, are largely members of the dnaE1|polV group.

Conclusion

Our studies provide several lines of evidence indicating that DNA polymerase III α
subunit and its isoforms participating in either replication (such as polC) or SOS mutagenesis/translesion synthesis (such as dnaE2), play dominant roles in determining GC variability. Other environmental or bacteriological
factors, such as genome size, temperature, oxygen requirement, and habitat, either
play subsidiary roles or rely indirectly on different mutator genes to fine-tune the
GC content. These results provide a comprehensive insight into mechanisms of GC content
variation and the robustness of eubacterial genomes in adapting their ever-changing
environments over billions of years.

Reviewers

This paper was reviewed by Nicolas Galtier, Adam Eyre-Walker, and Eugene Koonin.